Akao Takahiko, Takeyoshi Izumi, Totsuka Osamu, Arakawa Kazuhisa, Muraoka Masato, Kobayashi Katsumi, Konno Kenjiro, Matsumoto Koshi, Morishita Yasuo
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
J Heart Lung Transplant. 2006 Aug;25(8):965-71. doi: 10.1016/j.healun.2006.03.004. Epub 2006 Jun 5.
Free radical scavengers and superoxide dismutase have been found to protect against cerebral ischemic damage, and it was suggested that oxygen free radicals contribute to ischemia-reperfusion injury induced by cerebral ischemic damage. MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) is a potent scavenger and inhibitor of hydroxyl radicals and protective agent of peroxidative injury. The purpose of this study was to evaluate the effects of MCI-186 on pulmonary ischemia-reperfusion injury in a simulated transplanted lung model.
Fourteen dogs were divided into two groups (n = 7 each). In the MCI group, MCI-186 was continuously administered at 3 mg/kg/hour intravenously (IV) from 30 minutes before reperfusion until 30 minutes after reperfusion (total administration time 1 hour). Vehicle was administered in the control group. Warm ischemia was induced for 3 hours by clamping the left pulmonary artery and veins. Simultaneously, the left stem bronchus was bisected and then anastomosed before reperfusion. The right pulmonary artery was ligated 15 minutes after reperfusion, and the right stem bronchus was then bisected.
The respiratory gas exchange, hemodynamic changes, wet-to-dry weight ratio (WDR) and malondialdehyde (MDA) concentration in the tissue were significantly improved (p < 0.05) in the MCI group. The histologic damage was more severe in the control group and polymorphonuclear neutrophil (PMN) infiltration was reduced in the MCI group.
MCI-186 has a protective effect on pulmonary ischemia-reperfusion injury through the inhibition of lipid peroxidation.
已发现自由基清除剂和超氧化物歧化酶可预防脑缺血损伤，提示氧自由基参与脑缺血损伤所致的缺血再灌注损伤。MCI-186（3-甲基-1-苯基-2-吡唑啉-5-酮）是一种强效的羟自由基清除剂和抑制剂，也是过氧化损伤的保护剂。本研究旨在评估MCI-186在模拟移植肺模型中对肺缺血再灌注损伤的影响。
14只犬分为两组（每组n = 7）。MCI组在再灌注前30分钟至再灌注后30分钟（总给药时间1小时）以3 mg/kg/小时的速度静脉持续输注MCI-186。对照组给予溶媒。通过钳夹左肺动脉和肺静脉诱导3小时的热缺血。同时，在再灌注前将左主支气管切断并吻合。再灌注15分钟后结扎右肺动脉，然后将右主支气管切断。
MCI组的呼吸气体交换、血流动力学变化、组织湿干重比（WDR）和丙二醛（MDA）浓度均有显著改善（p < 0.05）。对照组的组织学损伤更严重，MCI组的多形核中性粒细胞（PMN）浸润减少。
MCI-186通过抑制脂质过氧化对肺缺血再灌注损伤具有保护作用。
